How apicomplexan parasites move in and out of cells

Abstract

Apicomplexan parasites utilize a unique form of 'gliding motility' to traverse across substrates, migrate through tissues, and invade into and finally egress from their vertebrate host cells. Parasite gliding relies on the treadmilling of surface adhesins linked to short actin filaments that are translocated rearward by stationary small myosin motors. New details reveal mechanistic insight into the coordinated release and processing of adhesins, the complexity of adhesin-substrate interactions, the regulation of the actin-myosin motor complex, and the formation of a novel junction at the host-parasite interface. These activities are carefully orchestrated to provide an efficient process for motility that is essential for parasite survival. The parasite-specific nature of many of these steps reveals several essential points that may be targeted for intervention.

Figure 1

Schematic depiction of intracellular cycle of T. gondii tachyzoites, which are representative of the invasive stages of most apicomplexans. A) Microneme secretion is required for gliding motility, cell attachment, and invasion, which are all powered by the parasite’s actin-myosin cytoskeleton. Gliding results in deposits of trails comprised of surface membrane proteins on the substratum (SAG1). During the initial contact with host cells, microneme secretion is stimulated by increases in intracellular calcium causing release of adhesive proteins at the apical end of the cell (i.e. MIC2). B) During invasion, discharge of rhoptry proteins results in formation of small vesicles within the host cell cytoplasm known as evacuoles [55]. In the electron micrograph at the lower left, the vacuole membrane is marked by arrows, while immunogold staining detects ROP1. C) Following formation of a tight junction, mediated by rhoptry neck proteins (i.e. RON4)(red ring), the parasite squeezes into the parasitophorous vacuole, which forms by invagination of the host cell membrane. The contents of rhoptries also decorate the PV membrane and fill the lumen as shown by immunofluorescence staining (i.e. ROP1 in the central top panel). D) Intracellular replication occurs by binary fission the parasite to form a rosette of daughter cells within the vacuole. E) The parasite actively egresses from the host cell, a process triggered by elevated calcium. Egress also requires microneme secretion, and is powered by the actin-myosin cytoskeleton, much the same as cell invasion. (Graphic drawing provided by S. Lourido, electron micrographs provided by W.L. Beatty, remaining panels adapted with permission from [2,18,27,55]).